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Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen
Biochemical Journal ( IF 4.4 ) Pub Date : 2021-09-17 , DOI: 10.1042/bcj20210476
Jennifer M Crowther 1 , Letitia H Gilmour 1 , Benjamin T Porebski 2 , Sarah G Heath 3 , Neil R Pattinson 4 , Maurice C Owen 4 , Rayleen Fredericks 1 , Ashley M Buckle 5 , Conan J Fee 1 , Christoph Göbl 3 , Renwick CJ Dobson 1
Affiliation  

Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen's Cys18–Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope for the antibody to the N-terminal region of angiotensinogen. We therefore provide evidence that the different redox forms of angiotensinogen can be detected by an antibody-based detection method.

中文翻译:

氧化还原开关的分子基础:分子动力学模拟和表面等离子体共振提供对还原和氧化血管紧张素原的洞察

血管紧张素原通过调节控制血压的血管紧张素肽的释放来微调肾素-血管紧张素系统的严格控制的活动。实现这种调节的一种机制是通过血管紧张素原的 Cys18–Cys138 二硫键作为氧化还原开关。血管紧张素原每种氧化还原状态的分子动力学模拟揭示了还原形式和氧化形式之间的细微动态差异,尤其是在 N 端。表面等离子共振数据表明,血管紧张素原的两种氧化还原形式显示出与固定化抗血管紧张素原单克隆抗体不同的结合动力学。质谱法将抗体的表位映射到血管紧张素原的 N 端区域。
更新日期:2021-09-15
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